The major mediators of nicotine's cognitive and addictive effects are nicotinic acetylcholine receptors (nAChRs). Stimulation of the ?42 receptor subtype is generally considered responsible for many reward- associated properties of nicotine. However, ?7 type nAChRs appear to share control over nicotine-associated dopamine efflux and self-administration behaviors. Furthermore, data indicate that ?7 subunits may underlie the cognitively enhancing effects of nicotine. Taken together, these findings suggest ?7 manipulation may positively affect a number of neurobehavioral endpoints relevant to effective nicotine cessation. Previous work with a novel ?7 partial agonist, GTS-21, has demonstrated it has neurocognitive benefits in other clinical, but non-smoking, populations. To the best of our knowledge, neither its neurocognitive effects, nor its effects on smoking behaviors have been systematically examined in chronic smokers without psychiatric comorbidities. Thus, this Phase 2 study will provide a necessary first step to measure the effects of GTS-21 on smoking, mood, neurocognitive performance, and brain electrophysiology in a small sample of currently healthy, chronic smokers. Because smoking maintenance and cessation are particularly poorly understood among women, every effort will be made to recruit sufficient numbers of women for preliminary sex comparisons. Using a double-blind, placebo controlled parallel group design, 54 (27 women) community smokers who have been screened to exclude those with major psychiatric disorders and/or significant medical disorders and who have a demonstrated readiness to quit, will participate an 7 week active trial (plus screening and 1-week placebo run-in). With the exception that equal numbers of each sex must be assigned to each group, subjects will be randomly assigned to 75 mg/twice a day (BID), 150 mg/BID, or placebo/ BID. Across the study period, participants will undergo repeated neurobehavioral testing, laboratory assessments of cardiovascular and liver function, and provide weekly updates regarding smoking behavior and mood state. Existing studies of persons with major psychiatric disorders reflect the safety of the drug at these doses. Therefore, although safety data will be collected throughout the trial, the primary focus is on providing preliminary efficacy data across smoking-related neurobehavioral domains (i.e., cigarette use, mood/affect, cognition). As a preliminary study, statistical power will be necessarily limited. However, these data will guide future research wherein alternative doses, exposure time, drug alternatives and/or drug combinations would be considered.